The objective of our proposal is to develop a model f myocardial infarction which can be extended by manipulations which would increase the ischemia iun the same territory as the native blood supply of the original infarct. The two infarcts will be pathologically distinguishable so that the direction of spread and extent of the infarct extension can be determined. We will observe and quantitate the direction of extension of the infarct both transmurally and laterally in an attempt to define the nature of a lateral border zone surrounding an acute myocardial infarct. Using dogs, an initial subendocardial infarct will be produced by temporary snaring the anterior descending coronary artery for 40 minutes. Catheters will be implaned in the carotid artery and left atrium for radionuclide microsphere blood flow studies and hemodynamic monitoring. Extension of the original subendocardial infarct will be produced by reoccluding the same vessel 7 days later. The dog will be sacrificed 24 hours later and the coronary arteries subtending the infarcted muscle and normal myocardium will be separately filled with different colored silicone rubber compounds (Microfil) to define the region at risk. The hearts will be fixed and section cut for histology and gamma counting for quantitation of infarction and myocardial blood flows. The extension of myocardial infarction will be investigated by comparing the region at risk defined by in vivo filling of the capillary beds with Microfil with histological evidence of old (8 days) and new (24 hour) necrosis. In the second phase of the experiments, it is proposed to produce the second infarct by occluding an adjacent coronary artery. Autoradiographic and histological staining methods will be used to distinguish the two infarcts. In the final phase, it is proposed to extend the original infarct by altering the oxygen supply/demand ratio within a short interval from the initiation of the first infarct.